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FLASH GENE
Symbol PHB contributors: mct/npt - updated : 24-10-2017
HGNC name prohibitin
HGNC id 8912
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • binding domain having the potential to fold into a coiled-coil structure
  • a PHB domain
    • conjugated PhosphoP
    HOMOLOGY
    interspecies homolog to murine Phb (99,63 pc)
    Homologene
    FAMILY
  • prohibitin family
    • CATEGORY tumor suppressor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,inner
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,nucleus,nucleoplasm
    text mainly localized to the inner mitochondrial membrane (Schleicher 2008)
    basic FUNCTION
  • potential tumor suppressor regulating E2F1 function
  • playing a role in the activation of the Ras-Raf signaling pathway and in modulating epithelial cell adhesion and migration
  • required for growth suppression by estrogen antagonists
  • having potential roles as a tumor suppressor, an anti-proliferative protein, a regulator of cell-cycle progression and in apoptosis
  • regulating membrane protein function by binding sterols, perhaps by altering their local lipid environment (Ross 2008)
  • important for mitochondrial function and prevents reactive oxygen species-induced senescence and thereby maintains the angiogenic capacity of endothelial cells (Schleicher 2008)
  • having diverse functions, such as the regulation of apoptosis and the maintenance of mitochondrial morphology (Matsuda 2008)
  • having a mitochondrial function that regulates the organization and maintenance of mitochondrial DNA (mtDNA)(Kasashima 2008)
  • membrane protein that is essential for cell proliferation and development in higher eukaryotes (Osman 2009)
    • CELLULAR PROCESS cell cycle, progression
    cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • prohibitin-1 (PHB) and prohibitin-2 (PHB2), form large, multimeric ring complexes in the inner membrane of mitochondria (Osman 2009)
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • PHB2
  • binding to the Rb protein as well as E2F and this binding was necessary to suppress cell proliferation
  • binding cholesterol
  • interacting with TFAM (maintains the organization and copy number of the mtDNA through both TFAM-independent and -dependent pathways) (Kasashima 2008)
  • PHB/PHB2 and the CD86 cytoplasmic domain cooperate to mediate CD86 signaling in a B cell through differential phosphorylation of distal signaling intermediates required to increase IGHG1
  • SIGLEC9 bound to prohibitins PHB, PHB2, in a sialic acid-independent manner
  • PHB can act as a signalling scaffold protein to assist in KDELR1, KDELR2-dependent Src activation
  • PHB in spermatocytes regulates the expression of STAG3, a key component of the meiotic cohesin complex, via a non-canonical JAK/STAT pathway
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in breast cancer
    tumoral     --over  
    in invasive adenocarcinoma
    constitutional        
    silencing of PHB blocks the formation of functional blood vessels (Schleicher 2008)
    constitutional     --low  
    loss of PHB in spermatocytes resulted in complete male infertility, associated with not only meiotic pachytene arrest with accompanying apoptosis, but also apoptosis resulting from mitochondrial morphology and function impairment
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target represent previously unrecognized therapeutic targets for regulating T cell activation, differentiation, viability, and function (Ross 2008)
    ANIMAL & CELL MODELS